tbuckley/cabot-search huggingface dataset:
Docetaxel-based triplet neoadjuvant therapy for esophageal adenocarcinoma: A comprehensive analysis of outcomes spanning over a decade.
Authors: James Tankel, Nabeel Ahmed, Thierry Alcindor, Jamil Asselah, Petr Kavan, Frederic Lemay, Dominique A. Frechette, Shelly Sud, Lawrence Lee, Sara Najmeh, Jonathan Spicer, Jonathan Cools-Lartigue, Carmen L. Mueller, Lorenzo Ferri
Journal: Journal of Clinical Oncology (2023)

332 Background: Docetaxel-based therapy is currently the most effective neoadjuvant regimen for locally advanced gastroesophageal adenocarcinoma. However, prior trials were primarily designed to target gastric cancer. As survival associated with taxane-based chemotherapy in esophageal adenocarcinoma (EAC) is less well described, we sought to review our experience with docetaxel based therapy as a neoadjuvant approach for EAC. Methods: A single centre retrospective review of a prospectively maintained upper GI cancer surgical database was performed (2008-2021). Patients with EAC undergoing curative intent neoadjuvant therapy with two similar docetaxel-based regimens (DCF - Docetaxel/Cisplatin/5FU or FLOT - 5FU, Leucovorin, Oxaliplatin, and Docetaxel) followed by en-bloc resection were included. Gastric/EGJ type III tumors were excluded. Clinicopathological data and overall survival (OS) were recorded and stratified by chemotherapy type (DCF vs FLOT). Data are presented as median (+/-SD). Mann-Whitney U tests for continuous or Fischer exact test for categorical variables determined significance. Kaplan-Meier curves compared OS. Results: 225 EAC patients were identified: Age 64.2 (±10.3) and tumor location was Esophageal/EGJ I/EGJ II (106/33/86). Clinical stage was cT3-4 in 201/225 (89.3%) and most were cN+ (200/225: 88.9%). There were 121 (53.7%) treated with neoadjuvant DCF whilst 104 (46.3%) received FLOT. All pre-op cycles were completed in 181 (80.4%) and did not differ between DCF and FLOT (81.8% vs 78.8% - NS). Operative procedure included Ivor Lewis in 188 (83.5%), left thoraco-abdominal esophagectomy in 20 (8.8%), and McKeown in 17 (7.5%) and also did not differ between DCF and FLOT. In terms of pathologic outcomes, the median lymph node yield was 35 (±16) of which 3.6±5.8 were positive). There was no difference when comparing between regimens. There were 134 (59.6%) patients ypN1-3 (DCF=76(62.8%) vs FLOT=58(55.8%)- NS). An R0 resection was achieved in 210 (93%) patients (DCF=92.6% vs FLOT=94.2%- NS). Complete pathological response (no residual cancer) was found in 21 patients (9.3%) (DCF=14(11.6%) vs FLOT=7(6.7%) – NS). At follow up of 41(±36) months (DCF= 52±41 vs FLOT=27±23 - p&lt;0.001) OS (KM curve Fig 1) at 1, 3 and 5 years for the entire cohort was 91.4%, 62.8%, and 55.7%, with no difference between DCF (92.3%/68.8%/59.5%) and FLOT (89.8%/54.5%/51.7% - NS). Conclusions: This retrospective review, the largest yet reported, demonstrates that these similar docetaxel-based neoadjuvant chemotherapy regimens are highly effective for patients with locally advanced esophageal adenocarcinoma.
Real-world outcomes with front-line doublet versus triplet chemotherapy in advanced gastroesophageal adenocarcinoma.
Authors: Shashank Sama, Christopher Duane Nevala-Plagemann, Jarrod Smith, Lisa M. Pappas, Benjamin Haaland, Ignacio Garrido-Laguna
Journal: Journal of Clinical Oncology (2023)

313 Background: Current guidelines recommend an upfront cytotoxic doublet with or without targeted therapy or immunotherapy for the management of patients with advanced gastroesophageal adenocarcinoma (aGEA).While evidence for the superiority of combination chemotherapy over single agent chemotherapy has been well established, the comparison of two drug versus three drug regimens has been less definitive. This study analyzed a large real-world database to compare clinical outcomes between doublet and triplet approaches in the frontline setting. Methods: The nationwide de-identified Flatiron Health electronic health record (EHR)-derived database was reviewed for patients with aGEA treated with a first line (1L) cytotoxic doublet or triplet irrespective of combination targeted therapy between 2011 and 2022. Patients who received non-standard chemotherapy combinations or did not have a visit or medication order within 90 days of advanced stage diagnosis were excluded. Kaplan Meier and Cox proportional hazards models were used to compare overall survival outcomes between groups. Overall survival was considered as time from the 1L therapy to death with censoring for loss to follow up. Results: 5375 patients with aGEA who met inclusion criteria, 4415 (82%) received doublet chemotherapy and 960 (17%) received triplet in the 1L. Median OS (mOS) for those receiving a doublet was 11 months (95%CI 10-11) similar to those receiving a triplet (11 months, 95% CI 10-12). A Cox proportional hazards model controlling for potential confounding variables of gender, race, smoking status, disease site, as well as HER2 and PDL1 status did not show a significant difference in outcomes between the two groups (HR 0.9, 95%CI 0.8-1). A subgroup analysis comparing FLOT with FOLFOX/CapeOx demonstrated an improved mOS with FLOT (13 mo vs 10 mo; 95%CI 11-15 vs 9-10). This benefit was sustained in a multivariable analysis which demonstrated an increased risk of death with FOLFOX/CapeOX compared to FLOT (HR 1.2, 95% CI 1-1.4). Conclusions: Consistent with prior studies, this real-world study did not identify a significant difference in survival outcomes with 1L triplet compared to doublet chemotherapy in aGEA. When limiting analysis to modern chemotherapy regimens however this data does suggest that a survival benefit may exist with the use of FLOT when compared to FOFOX/CapeOX. This finding would need to be further evaluated in prospective trials incorporating immunotherapy and targeted therapy prior to widespread recommendation.
Efficacy of atezolizumab/bevacizumab combination therapy in BCLC-C cirrhotic patients with hepatocellular carcinoma (HCC) according to the type of disease progression.
Authors: Spyridon Pantzios, Antonia Syriha, Dionysia Mandilara, Ioanna Stathopoulou, Georgia Barla, Petros Galanis, Ioannis Elelfsiniotis
Journal: Journal of Clinical Oncology (2023)

557 Background: HCC recurs in 70-80% of cases following potentially curative liver resection (LR) or radiofrequency ablation (RFA) and the immune component of the liver microenvironment plays a key role in early recurrence. The aim of our study was to retrospectively evaluate, under real life conditions, the overall survival (OS) of patients with advanced HCC (BCLC-C stage), either initially presented in the advanced stage or migrating from BCLC-A to BCLC-C stage within 2 years after curative LR or RFA, treated either with atezolizumab-bevacizumab (ATZ/BEV) combination or with TKIs sequentially (sorafenib as first line and cabozantinib as second line treatment). Methods: Sixty cirrhotic patients with advanced HCC (53 males, mean age 67y, 35% with diabetes, CPT-A=68.3%/CPT-B=28.3%, mean MELD/Na=11, ALBI grade I=28.3%/ALBI grade II=61.7%, 45% with varices) who either initially presented on the BCLC-C stage and were treated with ATZ/BEV (group A, N=19) or TKIs (group B, N=15) or who migrated from BCLC-A to BCLC-C stage within 2 years after LR or RFA and were treated with ATZ/BEV (group C, N=12) or TKIs (group D, N=14) were evaluated. Results: The four groups were comparable for all the baseline parameters evaluated (age p=0.9, gender p=0.1, platelets p=0.4, chronic liver disease etiology p=0.6, coexistence of diabetes p=0.3, presence of varices p=0.1, CPT stage p=0.1, ALBI grade p=0.3). Median OS was significantly higher for group C patients (mean survival 33.7m, median OS was not reached at the time of evaluation) compared to group D (mOS=27m), group A (mOS=13m) and group B (mOS=8m) patients, as presented in figure 1. It is important to note that the survival after HCC recurrence for group C patients (mean survival=18.2m, median OS was not reached at the time of evaluation) was significantly higher compared to those of group D patients (mOS=9m). Conclusions: Median survival of TKI-treated patients after HCC recurrence is less than 12m and is comparable to survivals observed in patients who initially classified in BCLC-C stage, irrespective of treatment schedule. ATZ/BEV combination therapy significantly prolongs survival in patients after early HCC recurrence, a finding that strongly supports the rationale for adjuvant ATZ/BEV therapy in high risk of recurrence patients.
Spectrum of germline mutations among Mexican patients with colorectal cancer.
Authors: Dione Aguilar, Sandra Santuario Facio, Angélica Barraza, Cynthia Villarreal-Garza, Rocio Ortiz Lopez
Journal: Journal of Clinical Oncology (2023)

78 Background: Colorectal cancer (CRC) is the third most common cancer in the world, and the second most frequent cause of death due to cancer. 5-10% of CRC cases are due to a hereditary predisposing syndrome, the most frequent being Lynch Syndrome (LS) followed by Familial Adenomatous Polyposis (FAP), characterized by loss of function of mismatch repair genes (MMR) and APC, respectively. The purpose of this study is to describe the spectrum of germline pathogenic variants among Mexican CRC patients using Next-generation sequencing (NGS). Methods: This study is original research approved by IRB; all patients signed the informed consent. 43 patients between 18-60 y/o with CRC were enrolled. NGS was performed using a panel which targeted a set of 94 genes and 284 SNPs known to play a role in cancer predisposing. Bioinformatics data analysis was carried out using Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE) and an in-silico analysis to classify variants according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Mean age 48.71 y/o, 62.6% men. Germline pathogenic and likely pathogenic variants (PV/LP) were identified in 69% of sample. A molecular diagnosis of LS (MLH1, MSH2, MSH6, and PMS2) was confirmed in 12 (28%), and FAP in 5 (11.6%). It is remarkably the presence of 5 PV in PRF1 (2 G149S; 3 A91V), among other unusual genes for CRC. Also 12 double heterozygotes were identified, including one with PRF1 and CHEK2 PV. Conclusions: NGS allow the discover of new pathogenic variants that would not be suspected in classic hereditary syndromes. The understanding of other genes involved in other pathways could expand our understanding in the heritability of CRC. PRF1 emerges as a new candidate gene associated with CRC, previous evidence supports the role of PRF1 in solid tumors beside hematologic malignancies.
Report of adverse events of special interest (AESIs) for sintilimab plus a bevacizumab biosimilar (IBI305) in unresectable hepatocellular carcinoma.
Authors: Zhenggang Ren, Jianming Xu, Yuxian Bai, Aibing Xu, Shundong Cang, Chengyou Du, Baorui Liu, Qiu Li, Yinying Lu, Yajin Chen, Guoliang Shao, Yabing Guo, Zhendong Chen, Jia Fan
Journal: Journal of Clinical Oncology (2023)

530 Background: In the phase III Orient-32 trial (NCT03794440), sintilimab plus IBI305 demonstrated a meaningful improvement in overall survival (OS) and progression-free survival (PFS) vs. sorafenib (Sor) in patients (pts) with unresectable HCC. Here we report the AESIs for sintilimab and IBI305 in Orient-32. Methods: 571 eligible pts with unresectable HCC were randomly assigned (2:1) to receive either sintilimab plus IBI305 or Sor (400 mg orally twice daily), until disease progression or unacceptable toxicity. The co-primary endpoints were OS and independent radiological review committee (IRRC)-assessed PFS according to RECIST 1.1. AESIs were defined by the sponsor and reported without judgement of causality. Analyses explored the incidence and severity of AESIs as well as correlation between AESIs and efficacy. Results: The safety set included 402 pts in the sintilimab plus IBI305 group and 184 pts in the Sor group. At the data cutoff on Dec 30th, 2021, the median follow-up time was 26.7 months. Any AESIs (≥1%) for sintilimab plus IBI305 group and Sor group occurred in 77.9% pts and 53.3% pts, respectively. The incidence of treatment-related grade 3-4 AESI for sintilimab+IBI305 was 31.3% and treatment-related serious AESI was 13.9%. The most common any AESIs were proteinuria (61.7% ), hypertension (41.8%), hemorrhage (15.4%) and hyperthyroidism (14.2%) (Table). In the characteristics of baseline, ages can be a predictor of the onset of proteinuria, hypertension and hyperthyroidism. In addition, the occurrence of of proteinuria and hypertension can be a predictor for a better survival. Conclusions: AESIs for sintilimab and IBI305 were tolerable and manageable in Orient-32 trial. Further, the incidence and severity of AESIs were consistent with the known safety profiles of the individual agents. Clinical trial information: NCT03794440 . [Table: see text]
Safety of drug-eluting beads transarterial chemoembolization under the combination therapy with immune checkpoint inhibitors in unresectable hepatocellular carcinoma.
Authors: Sung-Hua Chiu, Wei-Chou Chang, Chung-Bao Hsieh, An-Chieh Feng
Journal: Journal of Clinical Oncology (2023)

556 Background: To analyze the safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) under the combination treatment with immune checkpoint inhibitors (ICI) in unresectable hepatocellular carcinoma (HCC). Methods: In this retrospective single-institution study, 208 HCC patients (152 male and 56 female; mean age, 64.70±11.46 years) who received DEB-TACE between 2018.Nov and 2021.Dec were enrolled. There were 74.0% patients had Barcelona Clinic Liver Cancer stage B HCC, 90.4% were Child-pugh A patients, 63.0% patients had albumin-bilirubin (ALBI) grade 2, and 51.0% patients were up-to-seven out. Among them, 50 patients (24.0%) who received ICI with interval less than 30 days with DEB-TACE were categorized as DEB-ICI group; the remaining 158 patients (76.0%) were categorized as DEB group. ALBI grade before and 90 days after DEB-TACE were recorded to evaluate liver function change. Complications within 90 days after DEB-TACE were considered as TACE-related and were compared between two groups. Results: DEB-ICI group had significant higher incidence rate of liver abscess than DEB group (14.0% versus 5.1%, p=0.0337); other TACE-related complications showed no difference between two groups. There were 23.9% patients in DEB-ICI group had elevated ALBI grade after DEB-TACE, which revealed no difference in comparison with 22.4% in DEB group ( p=0.8460). Univariate analysis confirmed that combination with ICI was an independent risk factor of liver abscess formation after DEB-TACE (odds ratio = 3.0523, 95% confidence interval: 1.0474-8.8947, p=0.0409). Among DEB-ICI group, patients received ICI before DEB-TACE had a trend to have higher risk of liver abscess formation than those who received DEB-TACE before ICI (23.8% versus 6.9%, p-value=0.0922). Conclusions: Combination treatment of ICI with DEB-TACE with interval less than 30 days increased risk of liver abscess formation after DEB-TACE.
Food insecurity and gastrointestinal (GI) cancer mortality in the United States, 2015 to 2019.
Authors: S. M. Qasim Hussaini, Krista Y. Chen, Amanda L. Blackford, Fumiko Chino, Arjun Gupta
Journal: Journal of Clinical Oncology (2023)

788 Background: Food insecurity is a crucial but under-appreciated social determinant of health in GI cancers given high rates of cachexia where nutritional status may adversely impact functional status and outcomes. We investigated the impact of county-level food insecurity on age-adjusted mortality rates (AAMRs) from GI cancer. Methods: GI cancer-related deaths (ICD C15-26) were linked across US counties from 2015-2019 in the CDC WONDER database to county-level food insecurity measures from Feeding America and Census County Business Patterns databases. These included percent of individuals with food insecurity or on Supplemental Nutrition Assistance Program (SNAP) benefits, and the average cost/meal (USD) and density of local fast food/take-out restaurants. All measures were classified into quartiles based on distribution. AAMRs per 100,000 were compared between 1 st and 4 th quartiles for each measure using robust linear regression models with log scale and including the population size as weights. Results: There were 790,624 GI cancer deaths with overall AAMR 43.0 (68.5% age &gt;65y, 57.8% male, 12.9% non-Hispanic Black, 8.9% Hispanic, 82.4% urban, 33.6% colorectal, 27.7% pancreatic, 19.6% liver/biliary cancer). Highest AAMRs were noted for age &gt;65y, men, non-Hispanic White, and rural areas. AAMRs increased when moving from least to most insecure counties as defined by overall food insecurity, higher proportion of population on SNAP, or by higher local fast food density. AAMRs were lower in counties where cost per meal was higher. Association between AAMRs and all measures were strongest in younger adults (&lt;65y), men, and rural counties, while association between AAMR and fast food density was strong among non-Hispanic Black individuals. Conclusions: Our study highlights the most food insecure US counties also have higher GI cancer mortality with significant sociodemographic variation. Food insecurity may be a helpful proxy for county-level social vulnerability in driving GI cancer mortality. Our findings recognize an important relationship between nutrition and cancer mortality and should inform ongoing congressional policy on food insecurity and assistance.[Table: see text]
Pre-diagnostic delay among patients with curative esophageal and gastric cancer during the COVID-19 pandemic.
Authors: Xin Wang, Osvaldo Espin-Garcia, Yvonne Bach, Hiroko Aoyama, Lucy Xiaolu Ma, Carly C. Barron, Thais Baccili Cury Megid, Eric Xueyu Chen, Jonathan Yeung, Carol Jane Swallow, Savtaj Singh Brar, Rebecca KS Wong, Aruz Mesci, John Kim, Patrick Veit-Haibach, Sangeetha Kalimuthu, Raymond Woo-Jun Jang, Elena Elimova
Journal: Journal of Clinical Oncology (2023)

302 Background: The majority of esophageal and gastric cancers are diagnosed at an advanced stage with poor overall survival (OS), leading some to propose screening, even in countries with a low incidence. Whether diagnostic delay from symptom onset has any impact on OS is unclear. We investigated this question in the peri-COVID19 pandemic era. Methods: We retrospectively analyzed a cohort of 308 patients with esophageal, gastroesophageal junction, or gastric carcinoma treated with curative intent at the Princess Margaret Cancer Centre from January 2017 to December 2021. Clinical details pertaining to the initial presentation were determined through a retrospective chart review. OS was estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to assess the association between pre-diagnostic interval with OS adjusting for baseline patient characteristics. Results: The median interval from symptom onset to diagnosis was 98 days (IQR 47-169 days). Using a cox proportional hazard model, prolonged pre-diagnostic interval was not associated with worse OS (HR 1.00, P=0.62). Comparing patients diagnosed before and during the COVID19 pandemic, there was a notable increase in diagnostic delay with median pre-diagnostic interval increasing from 92 to 126 days (P=0.007). Median age at time of diagnosis was 69.6 during the pandemic vs 64.7 before the pandemic. Linear regression showed squamous cell histology was significantly associated with increasing time to initial diagnosis (P=0.04). Looking at other delay metrics, there were no changes in time interval from diagnosis to treatment during versus before the pandemic (median = 1.7 weeks for both), and there was no change in time from diagnosis to resection in those patients who underwent surgery. Conclusions: The COVID19 pandemic caused significant diagnostic delay for patients presenting with curative esophageal and gastric cancer. We found no evidence of pandemic-related health system delays in treatment, once a diagnosis was made. The lack of correlation of pre-diagnostic interval with OS may reflect underlying tumour biology as the driving force that determines prognosis.
Early tumor shrinkage as a predictor of survival in patients with locally advanced pancreatic cancer treated with modified FOLFIRINOX or gemcitabine plus nab-paclitaxel combination therapy: An exploratory analysis of JCOG1407.
Authors: Shun Tezuka, Masato Ozaka, Junji Furuse, Kohei Uemura, Yusuke Sano, Kohei Nakachi, Hiroshi Imaoka, Michiaki Unno, Hirofumi Shirakawa, Satoshi Shimizu, Naoya Kato, Yasushi Kojima, Keiji Sano, Makoto Ueno
Journal: Journal of Clinical Oncology (2023)

547 Background: Early tumor shrinkage (ETS) has been reported as a prognostic predictor of chemotherapy for colorectal cancer. However, few studies have examined the potential of ETS in chemotherapy for pancreatic cancer. Herein, we evaluated whether ETS could be a prognostic predictor in patients treated with modified FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) or GnP (gemcitabine plus nab-paclitaxel) for locally advanced pancreatic cancer (LAPC), as an exploratory analysis of JCOG1407, a randomized phase II selection design trial comparing modified FOLFIRINOX and GnP for LAPC. Methods: Of 126 patients enrolled in JCOG1407, 112 with measurable lesions were included in this exploratory analysis. ETS was defined as a ≥ 20% reduction in tumor diameter compared with baseline at the initial imaging assessment 6–10 weeks after initiating chemotherapy. Patients were divided into two cohorts based on their ETS status as described above: the ETS cohort that achieved ETS and the non-ETS cohort that failed to achieve ETS. The impact of ETS on overall survival (OS) was compared using multivariable Cox regression analysis in (ⅰ) the modified FOLFIRINOX group, (ⅱ) the GnP group, and (ⅲ) the overall population. Results: Herein, we included 55 patients in the modified FOLFIRINOX group and 57 in the GnP group. Notably, 14 (25.5%) and 24 (42.1%) patients achieved ETS in the modified FOLFIRINOX and GnP groups, respectively. In the modified FOLFIRINOX group, the median OS in the ETS and non-ETS cohorts was 2.5 and 1.7 years, respectively; the adjusted hazard ratio (HR) of the ETS to the non-ETS cohort for OS was 0.37 (95% confidence interval [CI], 0.15-0.93). In the GnP group, the median OS in the ETS and non-ETS cohorts was 2.0 and 1.7 years, respectively; the adjusted HR of the ETS to the non-ETS cohort for OS was 0.51 (95% CI, 0.26-1.01). In the overall population, the median OS in the ETS and non-ETS cohorts was 2.3 and 1.7 years, respectively; the adjusted HR of the ETS to the non-ETS cohort for OS was 0.45 (95% CI, 0.27-0.75). Conclusions: We noted a trend toward increased survival in patients who achieved ETS, suggesting that ETS may be a prognostic predictor in patients with LAPC treated with modified FOLFIRINOX or GnP.